Drug anticipation and drug addiction. The 1998 H. David Archibald Lecture

Environmental cues associated with drug use become capable of eliciting withdrawal symptoms, craving and relapse to drug self-administration. The phenomenon, although noted almost 150 years ago, has repeatedly been confirmed in epidemiological and experimental studies. Drug tolerance, which is closely correlated with withdrawal symptoms and craving, is also modulated by drug-associated environmental cues. The contribution of predrug cues to withdrawal and tolerance is emphasized in a Pavlovian conditioning analysis of drug administration. Drug-induced disturbances are modulated by homeostatic responses elicited by pharmacological stimulation. According to the conditioning analysis, we learn to anticipate the drug effect; corrective response (conditional compensatory responses) occur in the presence of situations and events that have been associated with the drug in the past. These conditional responses, seen in anticipation of drugs, importantly contribute to drug tolerance, failures of tolerance (enigmatic overdoses), and withdrawal symptoms. I review evidence indicating that a complete analysis of drug withdrawal and tolerance requires an appreciation of the contribution of Pavlovian conditioning.